Palladium-Catalyzed ortho -Monoacylation of Arenes with Aldehydes via 1,2,4-Benzotriazine-Directed C-H Bond Activation

Article abstract of DOI:10.1055/s-0039-1691564

An efficient palladium-catalyzed C-H bond functionalization/ ortho -monoacylation reaction of 3-aryl-1,2,4-benzotriazines with (hetero)aryl or alkyl aldehydes has been developed, which offers a facile and alternative strategy for direct modification and further diversification of 3-aryl-1,2,4-benzotriazines. Bioactive 1,2,4-benzotriazine has been employed as a novel directing group for the palladium-catalyzed regioselective monoacylation of sp ² C-H bond protocol with broad substrate scope and good functional group tolerance.

Full text of DOI:10.1055/s-0039-1691564

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2020, 52, A–J
paper
A
de
J. Liu et al.
Paper
Synthesis
Palladium-Catalyzed ortho-Monoacylation of Arenes with
Aldehydes via 1,2,4-Benzotriazine-Directed C–H Bond Activation
Jin Liua,d
Shaofen Jinc
Yingxing Zhoua
Dongmei Nia
Tingting Liua
Bingcun Cui*a
Gang Hua
Pd(OAc)2 (5 mol%)
TBHP (2 equiv)
N
N
N
N
O
R3
N
H
N
O
R1
R1
+
AcOH (0.5 equiv), xylene, air
110 °C, 8 h
H
R3
R2
R2
R1 = Me, i-Pr, Cl
R2 = Me, OMe, Cl
25 examples
50–85% yield
R
3 = aryl, heteroaryl, alkyl
Xin Yua
Guosheng Huang*b
bioactive 1,2,4-benzotriazine as the directing group
aryl, heteroaryl and alky aldehydes, good FG tolerance
open atmosphere
high regioselectivity
good yields
a Hubei Key Laboratory of Kidney Disease Pathogenesis and
Intervention, School of Medicine, Hubei Polytechnic Univer-
sity, Huangshi 435003, P. R. of China
easy to scale up
cbc_hbpu@163.com
b State Key Laboratory of Applied Organic Chemistry, College
of Chemistry and Chemical Engineering, Lanzhou University,
Lanzhou 730000, P. R. of China
hgs2368@163.com
c Graduate School, Hubei Normal University, Huangshi
435003, P. R. of China
d Huangshi Shi Xing Pharmaceutical Co., Ltd., Huangshi
435003, P. R. of China
Received: 30.11.2019
Accepted after revision: 17.12.2019
Published online: 10.02.2020
able tool in organic synthesis over the past two decades.10
In this area of research, transition-metal-catalyzed direct-
ing groups-assisted strategy is one of the most efficient
methods to facilitate the regioselective cleavage of C–H
bond and its further transformation.11 In view of the effi-
ciency of C–H bond activation/functionalization and the
importance of diaryl ketones in organic synthesis and bio-
logical activity,12 an attracted extensive attention has been
observed in ortho-acylation of the aromatic C–H bonds cat-
alyzed by several transition metals and assisted by various
heteroatom directing groups.13 Since Cheng’s group pio-
neered in developing a Pd-catalyzed oxidative coupling of
2-arylpyridines with benzaldehydes to give aryl ketones in
the presence of dioxygen as oxidant in 2009,14 much prog-
ress on the direct sp2 C–H bond oxidative acylation has
been achieved over the past few years.13,15 A wide range of
structures that contain heteroatoms, such as pyridine,16 azo
group,17 acyloxy/acyl,18 oxazolyl,19 acetamino,20 oxime,21
cyano,22 and others,23 have been extensively employed as
directing groups for ortho-C–H bond activation/acylation.
However, to the best of our knowledge, there is still no re-
port of the transition-metal-catalyzed C–H bond function-
alizations directed by 1,2,4-benzotriazine except the only
one example about palladium-catalyzed C–O bond forma-
tion reaction demonstrated by us in 2013.24 Compared with
simple pyridine and quinoline rings, 1,2,4-benzotriazine is
considered to be more challenging as a directing group in
transition-metal-catalyzed C–H functionalizations. 1,2,4-
Benzotriazine possesses two additional nitrogen atoms,
which both have a lone pair electrons that can coordinate to
DOI: 10.1055/s-0039-1691564; Art ID: ss-2019-h0453-op
Abstract An efficient palladium-catalyzed C–H bond functionaliza-
tion/ortho-monoacylation reaction of 3-aryl-1,2,4-benzotriazines with
(hetero)aryl or alkyl aldehydes has been developed, which offers a facile
and alternative strategy for direct modification and further diversifica-
tion of 3-aryl-1,2,4-benzotriazines. Bioactive 1,2,4-benzotriazine has
been employed as a novel directing group for the palladium-catalyzed
regioselective monoacylation of sp2 C–H bond protocol with broad sub-
strate scope and good functional group tolerance.
Key words palladium-catalyzed, acylation, aldehydes, 1,2,4-benzotri-
azine, C–H activation
The 1,2,4-benzotriazine and its derivatives are an im-
portant class of heterocyclic compounds that display a wide
range of biological activities, such as antimalarial,1 antitu-
mor,2 protein kinase modulatory,3 antimicrobial,4 antiviral,5
and herbicidal.6 For instance, 1,2,4-benzotriazine 1,4-diox-
ides (BTOs) are influential antitumor drug candidates.7 In
addition, 3-amino-1,2,4-benzotriazine 1,4-dioxide (tirapaz-
amine, TPZ) can act as an excellent bioactive hypoxia-selec-
tive anticancer drug.8 Because of such broad bioactivities of
1,2,4-benzotriazine derivatives, the synthesis, modification,
and development of promising drug leads based on this
kind of templates have been a topic of interest to medicinal
chemists and organic synthetic chemists in recent years.2,9
Direct functionalization of C–H bonds has undeniably
become a prominent field in contemporary organic chemis-
try, and has emerged as an increasingly powerful and reli-
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
J. Liu et al.
Paper
Synthesis
the transition-metal catalyst via a five or six-membered
metallacycle.25 Most importantly, this directing group is a
useful building block for the potentially bioactive 1,2,4-
benzotriazine derivatives and it offers a facile and promis-
ing strategy for direct functionalization of 3-aryl-1,2,4-ben-
zotriazines as well as their further diversification.
selective ortho-monoacylation of 3-aryl-1,2,4-benzotri-
azines via the direct sp2 C–H bond oxidative coupling
reactions with aryl and alkyl aldehydes in the presence of
tert-butyl hydroperoxide (TBHP) and air, affording various
1,2,4-benzotriazine derivatives bearing aryl ketones in
moderate to good yields (Scheme 1).
In the light of the above and as a part of our ongoing in-
terest in developing synthetic methods of bioactive hetero-
cycles,24,26 we disclose herein the palladium-catalyzed regio-
N
N
R1
N
O
N
Pd(OAc)2 (5 mol%), TBHP (2 equiv)
R1
N
O
R2
+
H
R3
N
R2
AcOH (0.5 equiv), xylene, air
110 °C, 8 h
R3
1
2
3
N
N
N
N
N
N
N
N
N
N
N
O
N
O
N
O
N
O
N
O
NO2
Br
CN
Cl
3aa, 85%
3ab, 75%
3ac, 80%
3ae, 62%
3ad, 66%
N
N
N
N
N
N
N
N
N
N
N
O
N
O
N
O
N
O
N
O
Me
Cl
O2N
O
O
Me
3ai, 63%
3aj, 71%
3ag, 76%
3ah, 50%
3af, 72%
N
N
N
N
N
N
N
N
N
N
N
O
N
O
N
O
N
O
N
O
Cl
O
NH
3an, 63%
3ao, 56%
3am, 60%
3al, 70%
3ak, 53%
N
N
Cl
N
N
N
N
Me
N
N
N
N
Me
N
O
N
O
N
O
N
O
N
O
Me
Me
∗
(
)
Cl
Cl
Cl
Cl
3ca, 65%
3ea, 63%
3ap, 51%
3ba, 68%
3da, 71%
N
N
Me
N
N
N
N
N
N
N
N
Me
Cl
Me
N
O
N
O
N
O
N
O
N
O
Cl
OMe
Cl
Cl
Cl
Cl
Cl
3ia, 72%
3fa, 66%
3ga, 62%
3ha, 70%
3ja, 81%
Scheme 1 Substrate scope of 3-aryl-1,2,4-benzotriazines 1 and aldehydes 2. Reagents and conditions: 1 (0.15 mmol), 2 (0.45 mmol), Pd(OAc)2
(5 mol%), TBHP (2 equiv), AcOH (0.5 equiv), and anhyd xylene (1 mL) with stirring at 110 °C under air atmosphere for 8 h. Isolated yields are given.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

C
J. Liu et al.
Paper
Synthesis
Initially, 3-phenyl-1,2,4-benzotriazine (1a) and 4-chlo-
robenzaldehyde (2a) were chosen as model substrates for
surveying the reaction conditions (Table 1). The impact of
the catalyst, oxidant, and solvent was investigated in detail
for the reaction (Table 1). When we performed the oxida-
tive coupling reaction of 1a and 2a with PdCl2 and TBHP at
110 °C in xylene, 3aa was isolated with 46% yield after 16
hours (Table 1, entry 1). In order to improve the yield, other
PdII catalysts such as PdCl2(PPh3)2 and Pd(OAc)2 instead of
PdCl2 were applied to the reaction, and Pd(OAc)2 promoted
the reaction in 68% yield of the desired product (entries 2
and 8). However, other screened metal catalysts such as Pd0
[Pd(dba)2, Pd2(dba)3 and Pd/C], FeCl3, and NiCl2(PPh3)2 all
gave unsatisfactory results (entries 3–7). Furthermore, a
better yield of the desired product 3aa (77%) was obtained
with the use of 0.5 equivalent of AcOH as additive (entry
9).15a And to our delight, the yield of 3aa could be further
improved from 77% to 86% when the reaction was carried
out exposed to air under the previous conditions (entries 9,
10). Additionally, when we shortened the reaction time
from 16 hours to 8 hours under the same reaction condi-
tions, the yield was almost unchanged (entries 10, 11). As
far as we know, aldehydes are usually sensitive to some oxi-
dants, so the choice of oxidants is also crucial for this oxida-
tive coupling reaction. Accordingly, several other oxidants
such as dioxygen, air, Oxone, Cu(OAc)2, and BQ (benzoqui-
none) were screened, respectively, for the desired product
3aa, but disappointingly, no better results were obtained
compared with TBHP (entries 12–16). Then, different sol-
vents such as toluene, DCE, DMF, acetonitrile, and 1,4-diox-
ane were also evaluated for the reaction, and those solvents
had a profound negative impact on the reaction (entries
17–21). The phenomenon suggested that xylene was the
best solvent of choice for the reaction. Finally, it should be
pointed out that when 3 equivalents of 2a were used, diacy-
lated product was not detected. It is perhaps because of the
electron-withdrawing effect and the steric hindrance of the
benzoyl on the monoacylation product, which both reduce
the reactivity of the secondary oxidative coupling. The ste-
ric effect of the benzoyl may hinder the arene from rotating
for the second cyclopalladation with the N4 atom. In addi-
tion, in the investigation of 1 mmol scale-up of this model
reaction, we found the main by-product of the reaction was
4-chlorobenzoic acid, which precipitated from the reaction
mixture after the reaction was cooled to room temperature
and 1.4 mmol of 4-chlorobenzoic acid was isolated by direct
filtration (Scheme 2). In other words, there was only a little
excessive amount of 4-chlorobenzaldehyde for the oxida-
tive acylation and this may also give an explanation for the
absence of the diacylated product in the reaction. Based on
these investigating experiments, we established the opti-
mized reaction conditions as 3-phenyl-1,2,4-benzotriazine
(1a; 0.15 mmol), 4-chlorobenzaldehyde (2a; 0.45 mmol),
Pd(OAc)2 (5 mol%), TBHP (2 equiv), AcOH (0.5 equiv), and
xylene (1 mL), with stirring at 110 °C under air atmosphere
for 8 hours (entry 11).
Table 1 Optimization of the Reaction Conditionsa
N
N
N
N
O
N
N
O
5 mol% cat., oxidant
solvent, 110 °C
H
+
Cl
1a
2a
Cl
3aa
Entry
Catalyst
PdCl2
Oxidant
Solvent
Yield (%)b
1
2
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
O2
xylene
xylene
xylene
xylene
xylene
xylene
xylene
xylene
xylene
xylene
xylene
xylene
xylene
xylene
46
43
PdCl2(PPh3)2
Pd(dba)2
Pd2(dba)3
Pd/C
3
<10
<10
n.d.
n.d.
n.d.
68
4
5
6
FeCl3
7
NiCl2(PPh3)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
8
9c
77
10d
11e
12
13
14
15
16
17e
18e
19e
20e
21e
86
85
56
air
38
Oxone
<10
<10
<10
73
Cu(OAc)2
BQ
xylene
xylene
toluene
DCE
TBHP
TBHP
TBHP
TBHP
TBHP
55
DMF
46
MeCN
52
1,4-dioxane
58
a Reaction conditions: 1a (0.15 mmol), 2a (0.45 mmol), catalyst (5 mol%),
oxidant (2 equiv), anhyd solvent (1 mL), 110 °C, 16 h, sealed reaction tube.
BQ: Benzoquinone.
b Isolated yield. n.d.: Not detected.
c With the additive of 0.5 equiv AcOH to the solvent.
d With the additive of 0.5 equiv AcOH to the solvent and the reaction was
performed exposed to air.
e With the additive of 0.5 equiv AcOH to the solvent; the reaction was per-
formed exposed to air and ran for 8 h.
Encouraged by the optimization results, we then set out
to explore the scope and generality of the reaction (Scheme
1). First, we tested a variety of aldehydes 2, and the detailed
results are summarized in Scheme 1. As can be seen from
Scheme 1, a variety of benzaldehydes 2a–k bearing either
electron-withdrawing or electron-donating groups could
react smoothly with 3-phenyl-1,2,4-benzotriazine (1a) un-
der the optimized conditions, affording the corresponding
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

D
J. Liu et al.
Paper
Synthesis
N
mation process. It is also worth noting that the chloro
group on the 3-aryl-1,2,4-benzotriazines was found to be
well compatible under the reaction conditions (3ca, 3ga).
The 1 mmol scale-up synthesis of [2-(benzo[e][1,2,4]tri-
N
N
O
azin-3-yl)phenyl](4-chlorophenyl)methanone
(3aa)
demonstrated the robustness of the method (Scheme 2). A
mixture of 3-phenyl-1,2,4-benzotriazine (1a; 1.0 mmol), 4-
chlorobenzaldehyde (2a; 3.0 mmol), Pd(OAc)2 (0.05 mmol),
and anhyd xylene (4 mL) was heated to 110 °C, then a solu-
tion of TBHP (2 mmol) in xylene (6 mL) was added drop-
wise into the mixture. The reaction mixture was kept under
stirring for 8 hours exposed to air. The corresponding prod-
uct 3aa was isolated in 81% yield (0.81 mmol, 0.28 g). The
method proved to be efficient in obtaining the product of
interest 3aa, with nearly no decrease in yield on a 1 mmol
scale. It should be pointed out that the main by-product 4-
chlorobenzoic acid (3b) precipitated from the reaction mix-
ture after the reaction was cooled to room temperature and
a small amount of the common decarbonylation by-product
was also observed from LC-MS in the 1 mmol scale-up of
the acylation experiment.
On the basis of the experimental results and previous
reports,14,15a,b,24,27 a plausible mechanism is proposed in
Scheme 3. First, the active palladium catalyst could react
with 1,2,4-benzotriazine(1a) to form a five-membered cy-
clopalladated intermediate A by chelation-directed C–H
bond activation on the arene. The intermedium pallada-
cycle A (PdII) could then react with the acyl radical B, gener-
ated in situ by hydrogen atom abstraction from the alde-
hyde 2, to afford the key PdIV or dimeric PdIII intermediate C
through oxidation in the presence of TBHP and air.15b,27g In
the process, TBHP plays the roles of both radical initiator
Cl
N
N
O
3aa (81% yield)
Pd(OAc)2 (5 mol%), TBHP (2 equiv)
AcOH (0.5 equiv), xylene, air
+
+
H
N
O
Cl
110 °C, 8 h
HO
↓
1a (1 mmol)
2a (3 mmol)
Cl
3b (1.4 mmol)
(precipitated from
the reaction mixture)
Scheme 2 Scale-up synthesis (1 mmol) of [2-(benzo[e][1,2,4]triazin-3-
yl)phenyl](4-chlorophenyl)methanone (3aa) under the optimized con-
ditions
desired products 3aa–ak in moderate to good yields (50–
85%). Subsequently, the target product 3al was obtained in
70% yield when 1-naphthaldehyde (2l) was employed as a
substrate for the reaction. In addition, the heteroaryl alde-
hydes such as pyrrole-2-aldehyde (2m) and furan-2-alde-
hyde (2n) could also be applied to afford the desired prod-
ucts. Notably, when the aliphatic aldehydes, for instance,
n-caprylic aldehyde 2o and citronellal (2p) were employed
for this transformation, the corresponding products 3ao
and 3ap were also formed in 56% and 51% yield, respectively.
Aromatic aldehydes have been shown to be much more
reactive than aliphatic aldehydes in the reaction. And it
could be found that a majority of benzaldehydes with
electron-withdrawing groups were superior to those with
electron-donating groups. Particularly, the benzaldehydes,
which have an electron-deficient substituent such as para-
chloro and para-bromo are more reactive in the reaction
(3aa, 3ac). However, lower yield of the product 3 was ob-
tained when these electron-deficient substituents were
changed into the stronger ones such as nitro and cyano
(3ad, 3ae, 3ah). Especially, the meta-nitro-substituted
benzaldehyde 2h gave the corresponding product 3ah in
only 50% yield. It should be emphasized that the chloro,
bromo, cyano, and nitro groups could all be well tolerated
in the reaction, which were favorable for further transfor-
mation.
N
O
R
N
N
N
3
N
H
N
Pd(OAc)2
1a
reductive
elimination
cyclopalladation
AcOH
AcOH
Subsequently, the scope with respect to 3-aryl-1,2,4-
benzotriazines 1 was surveyed under the optimized reac-
tion conditions. Satisfactorily, a series of 3-aryl-1,2,4-ben-
zotriazines 1 with either electron-donating or electron-
withdrawing substituents could be transformed smoothly
into the corresponding desired products 3ba–ja in good
yields (62–81%). We could observe obviously that electron-
donating groups on the 3-aryl-1,2,4-benzotriazines consid-
erably increased the yields of the corresponding products.
However, the product 3ea, which has two electron-donating
groups on the benzene ring was obtained in a lower yield
(63%), possibly because of the steric effect in this transfor-
N
N
N
N
N
N
putative
PdIII or PdIV
intermetiate
PdII
AcO
III/IV Pd
AcO
O
A
R
C
oxidation
TBHP, air
O
O
TBHP
H
R
R
B
2
Scheme 3 Proposed mechanism
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

E
J. Liu et al.
Paper
Synthesis
and oxidant,15b,27c while air assists the oxidation. Finally, the
resulting PdIII or PdIV intermediate C could undergo a subse-
quent reductive elimination to convert into the desired
ortho-acylation product 3 along with the regeneration of
the active palladium species to complete the catalytic cycle.
In summary, we have developed an efficient palladium-
catalyzed ortho-acylation reaction of 3-aryl-1,2,4-benzotri-
azines via direct C–H bond activation with (hetero)aryl and
alkyl aldehydes in the presence of TBHP and air. Multiple-
nitrogen-containing 1,2,4-benzotriazine, which is a useful
moiety for various potentially bioactive compounds, has
been explored as a directing group for this C–H functional-
ization protocol. Additionally, it offers a facile and alterna-
tive access to various 1,2,4-benzotriazine derivatives bear-
ing aryl ketones, which may be of importance in medicinal
chemistry for drug discovery processes. The applications of
1,2,4-benzotriazine as a directing group for more fields of
C–H activation and potential bioactivities screening of
these diversified 1,2,4-benzotriazine derivatives are under-
way in our laboratory.
13C NMR (100 MHz, CDCl3):  = 196.3, 159.1, 145.7, 140.7, 140.1,
138.8, 136.4, 135.7, 134.7, 130.9, 130.7, 130.5, 130.4, 129.5, 128.8,
128.6, 128.5.
HRMS (ESI): m/z [M + H]+ calcd for C20H13ClN3O: 346.0742; found:
346.0740.
[2-(Benzo[e][1,2,4]triazin-3-yl)phenyl](phenyl)methanone (3ab)
Yellow solid; yield: 35.0 mg (75%); mp 117–119 °C.
IR (KBr): 3320, 3063, 2247, 1668, 1509, 1278, 1016, 931, 770, 709 cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.70 (d, J = 8.0 Hz, 1 H), 8.40 (d, J = 8.0
Hz, 1 H), 7.86 (t, J = 8.0 Hz, 1 H), 7.81–7.73 (m, 5 H), 7.69 (t, J = 8.0 Hz,
1 H), 7.61 (d, J = 8.0 Hz, 1 H), 7.35 (t, J = 8.0 Hz, 1 H), 7.28 (d, J = 8.0 Hz,
2 H).
13C NMR (100 MHz, CDCl3):  = 197.5, 159.3, 145.6, 141.1, 140.0,
137.9, 135.5, 134.9, 132.4, 130.8, 130.6, 130.3, 130.2, 129.4, 129.2,
129.0, 128.6, 128.2.
HRMS (ESI): m/z [M + H]+ calcd for C20H14N3O: 312.1132; found:
312.1129.
[2-(Benzo[e][1,2,4]triazin-3-yl)phenyl](4-bromophenyl)metha-
none (3ac)
Yellow solid; yield: 46.8 mg (80%); mp 56–58 °C.
IR (KBr): 3325, 3064, 2247, 1671, 1509, 1279, 1014, 928, 771 cm–1
.
Melting points were determined using an XT–4 melting point appara-
tus and are uncorrected. 1H NMR and 13C NMR spectra were deter-
mined in CDCl3 on a Varian-Inova 400 MHz with TMS as an internal
standard. IR spectra were obtained on Nicolet NEXUS 670 FT-IR in-
strument and only major peaks were reported in cm–1. HRMS data
were performed on Bruker Apex II mass instrument (ESI). Copies of
their 1H NMR and 13C NMR spectra are provided in the Supporting In-
formation. Column chromatography was performed with 200–300
mesh silica gel using flash column techniques. Xylene was distilled
over sodium. 3-Aryl-1,2,4-benzotriazines were prepared according to
our reported literature methods26d (see Supporting Information for
details). Other materials were purchased from common commercial
sources and used without additional purification.
1H NMR (400 MHz, CDCl3):  = 8.71 (d, J = 8.0 Hz, 1 H), 8.41 (d, J = 8.0
Hz, 1 H), 7.88 (t, J = 8.0 Hz, 1 H), 7.80–7.73 (m, 3 H), 7.70–7.66 (m, 3
H), 7.57 (d, J = 8.0 Hz, 1 H), 7.42 (d, J = 8.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 196.3, 159.0, 145.7, 140.5, 140.0,
136.8, 135.7, 134.6, 131.5, 130.9, 130.7, 130.6, 130.4, 129.4, 128.7,
128.4, 127.5.
HRMS (ESI): m/z [M + H]+ calcd for C20H13BrN3O: 390.0237; found:
390.0235.
4-[2-(Benzo[e][1,2,4]triazin-3-yl)benzoyl]benzonitrile (3ad)
Yellow solid; yield: 33.3 mg (66%); mp 188–190 °C.
IR (KBr): 3336, 3066, 2230, 1676, 1509, 1273, 1018, 932, 772 cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.76 (dd, J = 8.0, 0.8 Hz, 1 H), 8.43 (dd,
J = 8.0, 0.8 Hz, 1 H), 7.94–7.89 (m, 3 H), 7.84–7.78 (m, 3 H), 7.73 (tt, J =
8.0, 1.2 Hz, 1 H), 7.61–7.57 (m, 3 H).
13C NMR (100 MHz, CDCl3):  = 195.7, 158.6, 145.8, 141.4, 140.0,
139.9, 136.0, 134.6, 132.2, 131.2, 131.0, 130.9, 130.4, 129.5, 129.3,
128.8, 128.3, 118.0, 115.5.
Palladium-Catalyzed ortho-Monoacylation of 3-Aryl-1,2,4-Benzo-
triazines 1 with Aldehydes 2; General Procedure
A 10 mL oven-dried reaction tube was charged with 3-aryl-1,2,4-ben-
zotriazine 1 (0.15 mmol), aldehyde 2 (0.45 mmol), Pd(OAc)2 (1.7 mg,
0.0075 mmol) and anhyd xylene (1 mL). Then the reaction tube was
immersed in an oil bath at 110 °C. TBHP (60 L, 0.3 mmol) was added
dropwise with a syringe and the reaction was kept under stirring for
8 h exposed to the air. After the completion of the reaction monitored
by TLC analysis, the solvent was evaporated under reduced pressure
and the residue was directly purified by flash column chromatogra-
phy on a silica gel, eluting with PE/EtOAc (v/v, 10:1) to afford the de-
sired product 3 in moderate to good yield (50–85%).
HRMS (ESI): m/z [M + H]+ calcd for C21H13N4O: 337.1084; found:
337.1081.
[2-(Benzo[e][1,2,4]triazin-3-yl)phenyl](4-nitrophenyl)metha-
none (3ae)
Yellow solid; yield: 33.1 mg (62%); mp 180–182 °C.
IR (KBr): 3362, 2923, 1678, 1523, 1344, 1274, 1017, 932, 770, 712 cm–1
.
[2-(Benzo[e][1,2,4]triazin-3-yl)phenyl](4-chlorophenyl)metha-
1H NMR (400 MHz, CDCl3):  = 8.80 (d, J = 8.0 Hz, 1 H), 8.43 (d, J = 8.0
Hz, 1 H), 8.14 (d, J = 8.0 Hz, 2 H), 7.98 (d, J = 8.0 Hz, 2 H), 7.93 (t, J = 8.0
Hz, 1 H), 7.84–7.80 (m, 3 H), 7.75 (t, J = 8.0 Hz, 1 H), 7.62 (d, J = 8.0 Hz,
1 H).
13C NMR (100 MHz, CDCl3):  = 195.5, 158.5, 149.7, 145.8, 142.9,
140.0, 139.8, 136.0, 134.5, 131.3, 131.0, 130.5, 129.8, 129.6, 128.8,
128.3, 123.6.
none (3aa)
Yellow solid; yield: 44.1 mg (85%); mp 105–107 °C.
IR (KBr): 3396, 2924, 1670, 1508, 1278, 1090, 929, 770 cm–1
1H NMR (400 MHz, CDCl3):  = 8.72 (d, J = 8.0 Hz, 1 H), 8.44 (d, J = 8.0
Hz, 1 H), 7.90 (t, J = 8.0 Hz, 1 H), 7.81 (d, J = 8.0 Hz, 2 H), 7.78–7.75 (m,
3 H), 7.69 (t, J = 8.0 Hz, 1 H), 7.58 (d, J = 8.0 Hz, 1 H), 7.26 (d, J = 8.0 Hz,
2 H).
.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

F
J. Liu et al.
Paper
Synthesis
HRMS (ESI): m/z [M + H]+ calcd for C20H13N4O3: 357.0982; found:
HRMS (ESI): m/z [M + H]+ calcd for C21H16N3O: 326.1288; found:
357.0977.
326.1294.
[2-(Benzo[e][1,2,4]triazin-3-yl)phenyl](p-tolyl)methanone (3af)
Benzo[d][1,3]dioxol-5-yl[2-(benzo[e][1,2,4]triazin-3-yl)phe-
nyl]methanone (3aj)
Yellow solid; yield: 35.1 mg (72%); mp 56–58 °C.
Yellow solid; yield: 37.8 mg (71%); mp 86–88 °C.
IR (KBr): 3348, 2921, 1660, 1505, 1442, 1259, 1037, 771 cm–1
IR (KBr): 3312, 2923, 1666, 1510, 1278, 1016, 931, 771 cm–1
.
.
1H NMR (400 MHz, CDCl3):  = 8.70 (dd, J = 8.0, 0.8 Hz, 1 H), 8.43 (d, J =
8.0 Hz, 1 H), 7.88 (tt, J = 8.0, 1.2 Hz, 1 H), 7.83–7.76 (m, 3 H), 7.75–7.66
(m, 3 H), 7.60 (dd, J = 8.0, 0.8 Hz, 1 H), 7.09 (d, J = 8.0 Hz, 2 H), 2.28 (s,
3 H).
13C NMR (100 MHz, CDCl3):  = 197.3, 159.4, 145.7, 143.2, 141.4,
140.1, 135.5, 135.4, 134.8, 130.7, 130.5, 130.4, 130.1, 129.4, 129.4,
129.0, 128.9, 128.7, 21.5.
1H NMR (400 MHz, CDCl3):  = 8.68 (d, J = 8.0 Hz, 1 H), 8.46 (d, J = 8.0
Hz, 1 H), 7.94–7.86 (m, 2 H), 7.83–7.79 (m, 1 H), 7.76–7.72 (m, 1 H),
7.68 (tt, J = 8.0, 1.2 Hz, 1 H), 7.56 (dd, J = 8.0, 0.8 Hz, 1 H), 7.44 (d, J =
1.6 Hz, 1 H), 7.29 (d, J = 1.6 Hz, 1 H), 6.65 (d, J = 8.0 Hz, 1 H), 5.96 (s, 2
H).
13C NMR (100 MHz, CDCl3):  = 195.9, 159.4, 151.4, 148.0, 145.7,
141.3, 140.2, 135.6, 134.7, 132.9, 130.7, 130.6, 130.4, 130.1, 129.5,
128.8, 128.7, 126.1, 108.7, 107.6, 101.7.
HRMS (ESI): m/z [M + H]+ calcd for C21H16N3O: 326.1288; found:
326.1294.
HRMS (ESI): m/z [M + H]+ calcd for C21H14N3O3: 356.1031; found:
356.1036.
[2-(Benzo[e][1,2,4]triazin-3-yl)phenyl](3-chlorophenyl)metha-
none (3ag)
[2-(Benzo[e][1,2,4]triazin-3-yl)phenyl](2-chlorophenyl)metha-
none (3ak)
Yellow solid; yield: 39.4 mg (76%); mp 138–140 °C.
IR (KBr): 3328, 3066, 2925, 2248, 1673, 1509, 1290, 1016, 910, 770,
Yellow solid; yield: 27.5 mg (53%); mp 144–146 °C.
734 cm–1
.
IR (KBr): 3345, 3065, 2923, 1676, 1508, 1294, 1015, 930, 769 cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.75 (d, J = 8.0 Hz, 1 H), 8.44 (d, J = 8.0
Hz, 1 H), 7.93–7.89 (m, 1 H), 7.85–7.76 (m, 4 H), 7.71 (tt, J = 8.0, 1.2
Hz, 1 H), 7.64 (dt, J = 8.0, 1.2 Hz, 1 H), 7.59 (dd, J = 8.0, 0.8 Hz, 1 H),
7.35 (dq, J = 8.0, 1.2 Hz, 1 H), 7.22 (t, J = 8.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3):  = 196.1, 159.0, 145.7, 140.4, 140.0,
139.7, 135.7, 134.7, 134.6, 132.4, 131.0, 130.7, 130.5, 130.4, 129.6,
129.5, 129.0, 128.8, 128.5, 127.3.
1H NMR (400 MHz, CDCl3):  = 8.46–8.43 (m, 2 H), 8.03 (d, J = 8.0 Hz, 1
H), 7.93 (tt, J = 8.0, 1.2 Hz, 1 H), 7.83–7.66 (m, 4 H), 7.51 (dd, J = 8.0,
1.6 Hz, 1 H), 7.23 (d, J = 8.0 Hz, 1 H), 7.15 (tt, J = 8.0, 1.6 Hz, 1 H), 7.07–
7.03 (m, 1 H).
13C NMR (100 MHz, CDCl3):  = 195.3, 160.2, 145.6, 140.8, 140.2,
137.0, 136.0, 135.5, 133.3, 132.0, 131.6, 131.2, 131.0, 130.9, 130.7,
130.6, 130.0, 129.4, 129.0, 126.2.
HRMS (ESI): m/z [M + H]+ calcd for C20H13ClN3O: 346.0742; found:
346.0740.
HRMS (ESI): m/z [M + H]+ calcd for C20H13ClN3O: 346.0742; found:
346.0740.
[2-(Benzo[e][1,2,4]triazin-3-yl)phenyl](3-nitrophenyl)metha-
none (3ah)
[2-(Benzo[e][1,2,4]triazin-3-yl)phenyl](naphthalen-1-yl)metha-
none (3al)
Yellow solid; yield: 26.7 mg (50%); mp 149–151 °C.
Yellow solid; yield: 38.0 mg (70%); mp 168–170 °C.
IR (KBr): 3308, 3059, 2924, 1662, 1509, 1284, 1016, 914, 775 cm–1
.
IR (KBr): 3491, 3082, 2925, 1673, 1530, 1348, 1286, 1083, 1015, 771,
707 cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.79 (d, J = 8.0 Hz, 1 H), 8.69–8.68 (m, 1
H), 8.44–8.42 (m, 1 H), 8.26–8.23 (m, 1 H), 8.12 (d, J = 8.0 Hz, 1 H),
7.94–7.90 (m, 1 H), 7.84–7.79 (m, 3 H), 7.74 (tt, J = 8.0, 1.2 Hz, 1 H),
7.60 (dd, J = 8.0, 0.8 Hz, 1 H), 7.51 (t, J = 8.0 Hz, 1 H).
1H NMR (400 MHz, CDCl3):  = 9.17 (d, J = 8.0 Hz, 1 H), 8.57 (d, J = 8.0
Hz, 1 H), 8.27 (dd, J = 8.0, 1.6 Hz, 1 H), 7.80–7.75 (m, 3 H), 7.71–7.63
(m, 5 H), 7.57–7.55 (m, 1 H), 7.52–7.48 (m, 2 H), 7.13 (t, J = 8.0 Hz, 1
H).
13C NMR (100 MHz, CDCl3):  = 195.1, 158.6, 148.3, 145.8, 140.1,
139.7, 139.7, 136.0, 134.5, 134.5, 131.2, 130.9, 130.6, 129.5, 129.5,
128.6, 128.4, 126.7, 123.8.
13C NMR (100 MHz, CDCl3):  = 198.7, 160.0, 145.4, 142.3, 139.9,
135.9, 135.3, 135.2, 133.6, 132.7, 131.0, 130.8, 130.7, 130.6, 130.3,
130.3, 130.2, 129.2, 128.7, 128.1, 127.9, 126.6, 126.3, 123.9.
HRMS (ESI): m/z [M + H]+ calcd for C20H13N4O3: 357.0982; found:
HRMS (ESI): m/z [M + H]+ calcd for C24H16N3O: 362.1288; found:
357.0977.
362.1291.
[2-(Benzo[e][1,2,4]triazin-3-yl)phenyl](m-tolyl)methanone (3ai)
[2-(Benzo[e][1,2,4]triazin-3-yl)phenyl](1H-pyrrol-2-yl)metha-
none (3am)
Yellow solid; yield: 30.7 mg (63%); mp 111–113 °C.
Dark-brown solid; yield: 27.0 mg (60%); mp 204–206 °C.
IR (KBr): 3275, 2924, 1621, 1399, 1328, 1016, 894, 765 cm–1
1H NMR (400 MHz, CDCl3):  = 9.67 (br, 1 H), 8.48 (q, J = 8.0 Hz, 2 H),
7.92 (q, J = 8.0 Hz, 2 H), 7.83–7.79 (m, 1 H), 7.77–7.72 (m, 2 H), 7.67 (t,
J = 8.0 Hz, 1 H), 6.95 (s, 1 H), 6.46 (s, 1 H), 6.07–6.05 (m, 1 H).
IR (KBr): 3377, 3063, 2923, 1667, 1510, 1283, 1015, 770, 725 cm–1
.
.
1H NMR (400 MHz, CDCl3):  = 8.69 (dd, J = 8.0, 0.8 Hz, 1 H), 8.43 (d, J =
8.0 Hz, 1 H), 7.91–7.88 (m, 1 H), 7.87–7.74 (m, 3 H), 7.71–7.65 (m, 1
H), 7.65–7.62 (m, 2 H), 7.57 (d, J = 8.0 Hz, 1 H), 7.15 (d, J = 8.0 Hz, 2 H),
2.27 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 197.7, 159.5, 145.6, 141.3, 140.1,
137.8, 135.5, 135.0, 133.2, 130.7, 130.5, 130.4, 130.2, 129.7, 129.4,
129.0, 128.6, 128.1, 126.7, 21.2.
13C NMR (100 MHz, CDCl3):  = 186.2, 160.7, 145.6, 140.5, 140.5,
135.5, 135.4, 132.4, 130.9, 130.5, 130.4, 130.3, 129.4, 129.2, 128.9,
124.7, 118.8, 110.8.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

G
J. Liu et al.
Paper
Synthesis
HRMS (ESI): m/z [M + H]+ calcd for C18H13N4O: 301.1084; found:
HRMS (ESI): m/z [M + H]+ calcd for C21H15ClN3O: 360.0899; found:
301.1081.
360.0902.
[2-(Benzo[e][1,2,4]triazin-3-yl)phenyl](furan-2-yl)methanone
[2-(7-Chlorobenzo[e][1,2,4]triazin-3-yl)phenyl](4-chlorophe-
(3an)
nyl)methanone (3ca)
Dark-green oil; yield: 28.5 mg (63%).
Yellow solid; yield: 37.2 mg (65%); mp 152–154 °C.
IR (neat): 3377, 3122, 2923, 1657, 1463, 1301, 1017, 767 cm–1
.
IR (KBr): 3328, 3068, 2924, 1672, 1589, 1503, 1409, 1279, 1090, 1013,
929, 840, 732 cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.64 (d, J = 8.0 Hz, 1 H), 8.46 (d, J = 8.0
Hz, 1 H), 7.92–7.91 (m, 2 H), 7.84–7.79 (m, 1 H), 7.77–7.73 (m, 1 H),
7.69–7.68 (m, 2 H), 7.38 (s, 1 H), 6.93 (d, J = 4.0 Hz, 1 H), 6.32 (dd, J =
4.0, 1.6 Hz, 1 H).
1H NMR (400 MHz, CDCl3):  = 8.71 (d, J = 8.0 Hz, 1 H), 8.43 (s, 1 H),
7.83 (dd, J = 8.0, 2.0 Hz, 1 H), 7.79–7.74 (m, 4 H), 7.71 (tt, J = 8.0, 0.8
Hz, 1 H), 7.58 (d, J = 8.0 Hz, 1 H), 7.28 (d, J = 8.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 184.7, 159.7, 153.1, 146.4, 145.7,
140.2, 139.8, 135.6, 135.2, 130.7, 130.7, 130.6, 130.6 129.4, 129.0,
128.8, 118.5, 112.0.
13C NMR (100 MHz, CDCl3):  = 196.1, 159.3, 145.6, 140.7, 139.0,
138.7, 137.0, 136.6, 136.3, 134.3, 131.2, 130.5, 130.5, 130.0, 128.9,
128.7, 128.1.
HRMS (ESI): m/z [M + H]+ calcd for C18H12N3O2: 302.0925; found:
HRMS (ESI): m/z [M + H]+ calcd for C20H12Cl2N3O: 380.0352; found:
302.0929.
380.0359.
1-[2-(Benzo[e][1,2,4]triazin-3-yl)phenyl]octan-1-one (3ao)
[2-(Benzo[e][1,2,4]triazin-3-yl)-5-methylphenyl](4-chlorophe-
nyl)methanone (3da)
Dark-brown oil; yield: 28.0 mg (56%).
Yellow solid; yield: 38.3 mg (71%); mp 156–158 °C.
IR (neat): 3373, 2926, 1697, 1509, 1457, 1324, 1015, 769 cm–1
.
IR (KBr): 3332, 3064, 2923, 1670, 1589, 1507, 1293, 1091, 1017, 837,
1H NMR (400 MHz, CDCl3):  = 8.57 (d, J = 8.0 Hz, 1 H), 8.47 (dd, J = 8.0,
1.2 Hz, 1 H), 8.06 (d, J = 8.0 Hz, 1 H), 8.00 (tt, J = 8.0, 1.6 Hz, 1 H), 7.88
(tt, J = 8.0, 1.2 Hz, 1 H), 7.69–7.60 (m, 2 H), 7.56 (dd, J = 8.0, 1.2 Hz, 1
H), 2.83 (t, J = 8.0 Hz, 2 H), 1.81–1.74 (m, 2 H), 1.33–1.25 (m, 8 H), 0.86
(t, J = 8.0 Hz, 3 H).
765 cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.65 (d, J = 8.0 Hz, 1 H), 8.41 (d, J = 8.0
Hz, 1 H), 7.87 (tt, J = 8.0, 1.2 Hz, 1 H), 7.79–7.75 (m, 4 H), 7.55 (d, J =
8.0 Hz, 1 H), 7.37 (s, 1 H), 7.25 (d, J = 8.0 Hz, 2 H), 2.52 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 206.3, 160.4, 146.0, 143.2, 140.5,
135.7, 134.0, 130.8, 130.6, 130.2, 130.0, 128.8, 127.2, 43.1, 31.7, 29.2,
29.1, 24.3, 22.6, 14.0.
13C NMR (100 MHz, CDCl3):  = 196.5, 159.0, 145.7, 141.8, 140.7,
140.1, 138.7, 136.6, 135.6, 131.8, 131.1, 130.5, 130.3, 129.5, 129.3,
128.6, 128.4, 21.5.
HRMS (ESI): m/z [M + H]+ calcd for C21H24N3O: 334.1914; found:
HRMS (ESI): m/z [M + H]+ calcd for C21H15ClN3O: 360.0899; found:
334.1916.
360.0902.
1-[2-(Benzo[e][1,2,4]triazin-3-yl)phenyl]-3,7-dimethyloct-6-en-1-
[2-(Benzo[e][1,2,4]triazin-3-yl)-4,6-dimethylphenyl](4-chloro-
one (3ap)
phenyl)methanone (3ea)
Dark-brown oil; yield: 27.5 mg (51%).
Yellow solid; yield: 35.3 mg (63%); mp 200–202 °C.
IR (neat): 3375, 2923, 1693, 1507, 1452, 1324, 1016, 770 cm–1
.
IR (KBr): 3336, 3063, 2924, 1672, 1587, 1509, 1264, 1090, 918, 758
cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.57 (d, J = 8.0 Hz, 1 H), 8.38 (d, J = 8.0
Hz, 1 H), 8.07 (d, J = 8 Hz, 1 H), 8.03–7.98 (m, 1 H), 7.89 (t, J = 8 Hz, 1
H), 7.69–7.59 (m, 3 H), 5.08 (t, J = 8 Hz, 1 H), 2.93–2.87 (m, 1 H), 2.74–
2.65 (m, 2 H), 2.28–2.12 (m, 2 H), 1.67 (s, 3 H), 1.56 (s, 3 H), 1.26 (t, J =
8 Hz, 2 H), 1.06–1.02 (m, 3 H).
1H NMR (400 MHz, CDCl3):  = 8.54 (s, 1 H), 8.43 (d, J = 8.0 Hz, 1 H),
7.87 (tt, J = 8.0, 1.2 Hz, 1 H), 7.81 (d, J = 8.0 Hz, 2 H), 7.76 (dd, J = 8.0,
1.2 Hz, 1 H), 7.69 (d, J = 8.0 Hz, 1 H), 7.33–7.31 (m, 3 H), 2.55 (s, 3 H),
2.25 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 205.3, 160.9, 146.0, 143.0, 140.5,
135.7, 134.6, 131.1, 130.6, 130.5, 129.7, 128.9, 127.5, 124.4, 49.8, 37.1,
35.3, 31.5, 29.2, 25.7, 25.5, 19.9, 17.6.
13C NMR (100 MHz, CDCl3):  = 197.4, 159.0, 145.8, 139.9, 139.5,
138.7, 137.3, 137.2, 136.1, 135.6, 134.4, 133.7, 130.5, 130.0, 129.4,
128.8, 128.5, 128.4, 21.3, 19.6.
HRMS (ESI): m/z [M + H]+ calcd for C23H26N3O: 360.2071; found:
HRMS (ESI): m/z [M + H]+ calcd for C22H17ClN3O: 374.1055; found:
360.2068.
374.1059.
(4-Chlorophenyl)[2-(7-methylbenzo[e][1,2,4]triazin-3-yl)phe-
[2-(Benzo[e][1,2,4]triazin-3-yl)-5-chlorophenyl](4-chlorophe-
nyl]methanone (3ba)
nyl)methanone (3fa)
Yellow solid; yield: 36.7 mg (68%); mp 153–155 °C.
Yellow solid; yield: 37.6 mg (66%); mp 150–152 °C.
IR (KBr): 3396, 2923, 1670, 1586, 1504, 1415, 1277, 1090, 1014, 929,
IR (KBr): 3333, 3066, 2922, 1673, 1590, 1507, 1262, 1088, 1016, 763
833, 739 cm–1
.
cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.70 (d, J = 8.0 Hz, 1 H), 8.18 (s, 1 H),
7.77–7.66 (m, 6 H), 7.57 (d, J = 8.0 Hz, 1 H), 7.24 (d, J = 8.0 Hz, 2 H),
2.61 (s, 3 H).
1H NMR (400 MHz, CDCl3):  = 8.73 (d, J = 8.0 Hz, 1 H), 8.45 (dd, J = 8.0,
0.4 Hz, 1 H), 7.92 (tt, J = 8.0, 1.6 Hz, 1 H), 7.84–7.72 (m, 5 H), 7.55 (d,
J = 2.0 Hz, 1 H), 7.31 (dt, J = 8.0, 2.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 196.3, 158.7, 145.8, 141.8, 140.5,
138.8, 138.7, 138.4, 136.5, 134.9, 130.8, 130.5, 130.4, 130.2, 128.8,
128.6, 128.0, 127.7, 22.0.
13C NMR (100 MHz, CDCl3):  = 194.6, 158.1, 145.8, 142.1, 140.0,
139.2, 137.7, 135.9, 135.9, 132.9, 131.7, 131.0, 130.5, 129.5, 128.8,
128.8, 128.5.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

H
J. Liu et al.
Paper
Synthesis
HRMS (ESI): m/z [M + H]+ calcd for C20H12Cl2N3O: 380.0352; found:
380.0359.
13C NMR (100 MHz, CDCl3):  = 196.4, 159.1, 152.2, 145.9, 140.8,
139.1, 138.5, 137.7, 136.8, 136.2, 135.0, 131.3, 130.8, 130.5, 129.0,
128.5, 128.1, 125.0, 34.3, 23.3, 21.5.
[2-(Benzo[e][1,2,4]triazin-3-yl)-4-chlorophenyl](4-chlorophe-
nyl)methanone (3ga)
HRMS (ESI): m/z [M + H]+ calcd for C24H21ClN3O: 402.1368; found:
402.1372.
Yellow solid; yield: 35.4 mg (62%); mp 122–124 °C.
IR (KBr): 3323, 3068, 2924, 1674, 1588, 1507, 1397, 1280, 1091, 928,
740 cm–1
.
Funding Information
1H NMR (400 MHz, CDCl3):  = 8.71 (d, J = 2.0 Hz, 1 H), 8.45 (dd, J = 8.0,
1.6 Hz, 1 H), 7.92 (dd, J = 8.0, 1.6 Hz, 1 H), 7.85–7.82 (m, 2 H), 7.74 (d,
J = 8.0 Hz, 2 H), 7.66 (dd, J = 8.0, 2.0 Hz, 1 H), 7.52 (d, J = 8.0 Hz, 1 H),
7.27 (d, J = 8.0 Hz, 2 H).
We thank the State Key Laboratory of Applied Organic Chemistry, Tal-
ent Introduction Project of Hubei Polytechnic University
(No.19XJK03R), and Medical School (HBPU) for financial support.
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3
R)
13C NMR (100 MHz, CDCl3):  = 195.2, 158.0, 145.9, 140.1, 139.1,
138.9, 136.7, 136.4, 136.1, 136.0, 131.2, 130.9, 130.5, 130.4, 130.2,
129.5, 128.8, 128.6.
Supporting Information
HRMS (ESI): m/z [M + H]+ calcd for C20H12Cl2N3O: 380.0352; found:
380.0359.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1691564.
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[2-(Benzo[e][1,2,4]triazin-3-yl)-4-methylphenyl](4-chlorophe-
nyl)methanone (3ha)
References
Yellow solid; yield: 37.8 mg (70%); mp 141–143 °C.
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Chem. Soc. 1954, 76, 3551.
IR (KBr): 3319, 3062, 2924, 1668, 1587, 1509, 1396, 1282, 1090, 933,
739 cm–1
.
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1H NMR (400 MHz, CDCl3):  = 8.49 (s, 1 H), 8.43 (d, J = 8.0 Hz, 1 H),
7.89 (t, J = 8.0 Hz, 1 H), 7.81 (t, J = 8.0 Hz, 2 H), 7.75 (t, J = 8.0 Hz, 2 H),
7.49 (s, 2 H), 7.24 (d, J = 8.0 Hz, 2 H), 2.59 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 196.3, 159.4, 145.7, 140.8, 140.1,
138.6, 137.9, 136.7, 135.7, 134.8, 131.5, 131.0, 130.6, 130.5, 129.5,
129.0, 128.5, 128.5, 21.5.
HRMS (ESI): m/z [M + H]+ calcd for C21H15ClN3O: 360.0899; found:
360.0902.
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2007, 41, 62.
(4-Chlorophenyl)[5-methoxy-2-(7-methylbenzo[e][1,2,4]triazin-
3-yl)phenyl]methanone (3ia)
Yellow solid; yield: 42.1 mg (72%); mp 158–160 °C.
(6) (a) Selby, T. P.; Denes, L. R.; Kilama, J. J.; Smith, B. K. Synthesis
and Chemistry of Agrochemicals IV; American Chemical Society:
Washington DC, 1995, Chap. 16, 171–185. (b) Selby, T. P. Patent
US 5389600, 1995.
IR (KBr): 3329, 3063, 2932, 1673, 1599, 1505, 1412, 1290, 1235, 1092,
1013, 833, 733 cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.73 (d, J = 8.0 Hz, 1 H), 8.14 (s, 1 H),
7.76 (d, J = 8.0 Hz, 2 H), 7.68 (dd, J = 8.0, 1.6 Hz, 1 H), 7.62 (d, J = 8.0 Hz,
1 H), 7.24 (dd, J = 8.0, 2.8 Hz, 3 H), 7.06 (d, J = 2.8 Hz, 1 H), 3.94 (s, 3 H),
2.59 (s, 3 H).
13C NMR (100 MHz, CDCl3):  = 195.9, 161.8, 158.2, 145.5, 142.2,
141.1, 138.8, 138.7, 138.2, 136.5, 131.8, 130.4, 128.6, 127.8, 127.7,
126.9, 115.9, 114.0, 55.7, 21.9.
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Lose, D.; Mark, C.; McPherson, A.; Palanki, M.; Pathak, V.;
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390.1002.
(4-Chlorophenyl)[2-(7-isopropylbenzo[e][1,2,4]triazin-3-yl)-4-
methylphenyl]methanone (3ja)
Yellow solid; yield: 48.9 mg (81%); mp 120–122 °C.
IR (KBr): 3324, 3060, 2964, 1671, 1587, 1505, 1428, 1280, 1090, 930,
842, 742 cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.48 (s, 1 H), 8.21 (d, J = 1.2 Hz, 1 H),
7.81 (d, J = 8.0 Hz, 2 H), 7.75–7.72 (m, 3 H), 7.49 (s, 1 H), 7.23 (d, J = 8.0
Hz, 2 H), 3.19–3.12 (m, 1 H), 2.59 (s, 3 H), 1.38 (d, J = 2.4 Hz, 3 H), 1.36
(d, J = 2.4 Hz, 3 H).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J

I
J. Liu et al.
Paper
Synthesis
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© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–J